• Subjects must meet all the following criteria to be eligible for enrollment into the study:

• Sign and date the informed consent form (ICF), prior to the start of any study-specific qualification procedures.

• Subjects ≥18 years of age or the minimum legal adult age (whichever is greater) at the time the ICF is signed

• HCC diagnosis confirmed by histology/cytology or clinically by American Association for Study of Liver Diseases (AASLD) 36 criteria in cirrhotic patients.

• At least one measurable untreated lesion per RECIST v1.1 (see Section 12). Patients who received prior liver directed therapy (ie., Trans arterial chemoembolization \[TACE\], Y-90, liver directed radiation etc.) are eligible provided the target lesion(s) have not been previously treated with liver directed therapy or the target lesion(s) within the field of local therapy have subsequently progressed in accordance with RECIST v1.1 (See Section 12)

• Locally advanced, metastatic, or unresectable disease.

• No prior systemic therapy for advanced HCC.

• Child Pugh Class A.

• Barcelona Clinic Liver Cancer (BCLC) Stage B (not amenable to liver directed therapy) or Stage C.

• ECOG Performance Status (PS) 0 or 1.

⁃ The following laboratory values obtained ≤ 28 days prior to registration. Local laboratory data must meet the following criteria at both Screening and prior to dosing on the planned Cycle 1 Day 1 visit to confirm relatively preserved organ function:

∙ Absolute neutrophil count (ANC) ≥1500/mm3

‣ Platelet count 100,000/mm3 (platelet transfusion is not allowed within 14 days prior to screening assessment).

‣ Hemoglobin (Hgb) 9.0 g/dL (red blood cell transfusion is not allowed within 14 days prior to screening assessment).

‣ Total bilirubin (TBIL) ≤1.5 x ULN.

‣ ALT and AST ≤3 x ULN

‣ For patients not receiving therapeutic anticoagulation INR or aPTT ≤2 x ULN

‣ Creatinine clearance ≥40 mL/min (measured by the Cockcroft-Gault equation)

⁃ If the subject is a female of childbearing potential, she must have a negative serum pregnancy test at Screening and must be willing to use highly effective birth control, as detailed in Section 4.4, upon enrollment, during the Treatment Period, and for 6 months, following the last dose of study drug. A female is considered of childbearing potential following menarche and until becoming postmenopausal (no menstrual period for a minimum of 12 months) unless permanently sterile (undergone a hysterectomy, bilateral salpingectomy or bilateral oophorectomy) with surgery at least 1 month before the first dose of study drug or confirmed by follicle stimulating hormone (FSH) test \>40 mIU/mL and estradiol \<40 pg/mL (\<140 pmol/L).

⁃ If male with partner of childbearing potential, the subject must be surgically sterile or willing to use highly effective birth control (Section 4.4) upon enrollment, during the Treatment Period, and for 6 months following the last dose of study drug.

⁃ Female subjects must not donate, or retrieve for their own use, ova from the time of screening and throughout the study treatment period, and for at least 6months after the final study drug administration.

⁃ Male subjects must not freeze or donate sperm starting at Screening and throughout the study period, and for at least 6 months after the final study drug administration.

⁃ Provide informed written consent ≤28 days prior to registration.

⁃ Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study).

⁃ Note: During the Active Monitoring Phase of a study (i.e., active treatment), participants must be willing to return to the consenting institution for follow-up.

⁃ Willing to provide mandatory blood specimens for correlative research purposes (see Section 10).

⁃ Unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to NCI-CTCAE v 5.0, Grade ≤1 or Baseline.

• Note: Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to \> Grade 2 for at least 3 months prior to enrollment and managed with standard of care treatment), which the Investigator deems related to previous anticancer therapy, composed of the following:

• Chemotherapy-induced neuropathy.

• Fatigue.

• Residual toxicities from prior immunotherapy treatment: Grade 1 or 2 endocrinopathies, which may include the following:

‣ Hypothyroidism/ hyperthyroidism.

⁃ Type I diabetes.

⁃ Hyperglycemia.

⁃ Adrenal insufficiency.

⁃ Adrenalitis.

⁃ Skin hypopigmentation (vitiligo).